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Flexibility as a Strategy in Nucleoside Antiviral Drug Design
- Source :
- Current Medicinal Chemistry. 22:3910-3921
- Publication Year :
- 2015
- Publisher :
- Bentham Science Publishers Ltd., 2015.
-
Abstract
- As far back as Melville Wolfrom's acyclic sugar synthesis in the 1960's, synthesis of flexible nucleoside analogues have been an area of interest. This concept, however, went against years of enzyme-substrate binding theory. Hence, acyclic methodology in antiviral drug design did not take off until the discovery and subsequent FDA approval of such analogues as Acyclovir and Tenofovir. More recently, the observation that flexible nucleosides could overcome drug resistance spawned a renewed interest in the field of nucleoside drug design. The next generation of flexible nucleosides shifted the focus from the sugar moiety to the nucleobase. With analogues such as Seley-Radtkequot;fleximersquot;, and Herdewijn's C5 substituted 2'-deoxyuridines, the area of base flexibility has seen great expansion. More recently, the marriage of these methodologies with acyclic sugars has resulted in a series of acyclic flex-base nucleosides with a wide range of antiviral properties, including some of the first to exhibit anti-coronavirus activity. Various flexible nucleosides and their corresponding nucleobases will be compared in this review.
- Subjects :
- Tenofovir
medicine.drug_class
Stereochemistry
Antiviral Agents
Biochemistry
Nucleobase
Drug Discovery
medicine
Humans
Simplexvirus
Sugar moiety
Pharmacology
Flexibility (engineering)
Chemistry
Fda approval
Organic Chemistry
HIV
Nucleosides
Area of interest
HIV Reverse Transcriptase
Drug Design
Reverse Transcriptase Inhibitors
Molecular Medicine
Antiviral drug
Nucleoside
medicine.drug
Subjects
Details
- ISSN :
- 09298673
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Current Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....6d72aebbf3a828328a0110a29787dcf9